Process for preparing isochroman compounds

ABSTRACT

High-purity isochroman compounds can be obtained in high yields according to a simple and economical process for preparing isochroman compounds, comprising the step of adding an aquesous solution of formaldehyde having a concentration of 40 to 70 wt. % to a complex of an arylalkanol represented by the following general formula (II) with a Friedel-Crafts catalyst to cyclize the arylalkanol: ##STR1## wherein R 1  and R 2  each stands for a hydrogen atom, a lower alkyl group or a lower alkoxyl group, or alternatively R 1  and R 2  are respectively bonded to adjacent carbon atoms with mutual bonding of R 1  and R 2  together with the carbon atoms respectively bonded to R 1  and R 2  to form a benzene ring, a naphthalene ring, or a C 5  or C 6  cycloalkane or cycloalkene which may have 1 to 6 lower alkyl groups; and R 3  stands for a hydrogen atom or a lower alkyl group.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a process for preparing isochromancompounds using an aqueous solution of formaldehyde having a specificconcentration as a formaldehyde source. The process of the presentinvention is simplified and economical.

2. Description of Related Art

It has been known to date that isochroman compounds represented by thefollowing general formula (I) have an excellent musky odor: ##STR2##wherein R₁ and R₂ each stands for a hydrogen atom, a lower alkyl groupor a lower alkoxyl group, or alternatively R₁ and R₂ are respectivelybonded to adjacent carbon atoms with mutual bonding of R₁ and R₂together with the carbon atoms respectively bonded to R₁ and R₂ to forma benzene ring, a naphthalene ring, or a C₅ or C₆ cycloalkane orcycloalkene which may have 1 to 6 lower alkyl groups; and R₃ stands fora hydrogen atom or a lower alkyl group.

Examples of the processes for preparing such isochroman compoundsinclude:

(1) a process comprising introducing hydrogen chloride gas into amixture of an arylalkanol and paraformaldehyde;

(2) a process comprising reacting an aromatic hydrocarbon compound withan alkylene oxide in the presence of aluminum chloride to form a complexof an arylalkanol with aluminum chloride, partially deactivating thealuminum chloride in the complex with a substance containing a freehydroxyl group, and adding paraformaldehyde to the resulting reactionmixture to cyclize the arylalkanol;

(3) a process comprising reacting an arylalkanol with an acetal in thepresence of a protonic acid;

(4) an improvement of the process described in the above item (3),comprising effecting the reaction in the presence of an azeotropic agentsuch as n-hexane, cyclohexane, methylcyclohexane, benzene or toluene;

(5) a process comprising adding chloride or oxychloride of sulfur orphosphorus to a mixture of an arylalkanol, concentrated hydrochloricacid and a compound capable of releasing formaldehyde; and

(6) a process comprising reacting an arylalkanol with formaldehyde inthe presence of a lower carboxylic acid anhydride or a methylene(lowercarboxylate) having lower alkyl moieties in the acyl groups thereof andan acid catalyst at a high temperature.

Since the these process involve respective demerits, however, they arenot well satisfactory as a process for preparing isochroman compounds.

More specifically, the process of the above item (1) involvesdisadvantages such as complicated operations, the necessity for the useof expensive and intractable hydrogen chloride gas, and the necessityfor the removal of water formed in keeping with the progress of thereaction out of the reaction system because of the incapability ofcompleting the reaction at the removal of water while lowering the yieldand involving side reactions.

On the other hand, the process of the above item (2) involvesdisadvantages such as generation of hydrogen chloride gas in anintermediate treatment step (the step of partially deactivating aluminumchloride in the complex), the necessity for the use of a limited amountof a deactivator, a low yield resulting from incompletion of thereaction and occurrence of side reactions, and complicated operations ina post-treatment step (the step of recovering the reaction product).

Further, the process of the above item (3) involves disadvantages suchas attainment of only an unsatisfactory yield despite the reactioneffected at a high temperature over a long time according to thisprocess, while the process of the above item (4) as an improvementthereof involves demerits such as a considerable cost involved in therecovery of an isochroman compound as the reaction product because ofthe use of an azeotropic agent.

Furthermore, the process of the above item (5) involves disadvantagessuch as generation of hydrogen chloride gas in the reaction system andattainment of only an unsatisfactory yield. On the other hand, theprocess of the above item (6) involves problems of complicatedoperations resulting from a high pressure of the reaction system becauseof the high-temperature reaction, and the necessity for the removal ofthe formed lower carboxylic acid out of the reaction system, as well asa demerit of attainment of only an unsatisfactory yield.

In view of the foregoing circumstances, the applicant has attempted thedevelopment of an improved process for preparing isochroman compounds.As a result, the applicant has found out and disclosed an improvedprocess for preparing isochroman compounds whereby isochroman compoundscan be prepared simply in good yields see Japanese Patent Laid-Open No.10,782/1988 (published on Jan. 18, 1988)!. This process comprisesreacting an arylalkanol with formaldehyde or a compound capable ofreleasing formaldehyde in a chlorinated hydrocarbon solvent in thepresence of a Friedel-Crafts catalyst having a dehydrating power.

Since, however, this process comprises first preparing an arylalkanolfrom an aromatic hydrocarbon compound, then separating it, and finallyderiving an isochroman compound from the arylalkanol, it is complicatedin steps and economically disadvantageous as compared with processes forsynthesizing isochroman compounds directly from aromatic hydrocarboncompounds. Moreover, in carrying out this process, for example,paraformaldehyde is used as the compound capable of releasingformaldehyde. However, the production of powdery paraformaldehyde isdoomed to be stopped because it deteriorates the working environmentinvolved in the production thereof, while granular paraformaldehydeentails a situation that it cannot be dissolved in the reaction systemand so scarcely advances the reaction.

DISCLOSURE OF THE INVENTION SUMMARY OF THE INVENTION

An object of the present invention is to provide a process for preparingisochroman compounds whereby high-purity isochroman compounds can beobtained in high yields.

Another object of the present invention is to provide a simplifiedeconomical process for preparing isochroman compounds wherebyhigh-purity isochroman compounds can be obtained in high yields.

The inventors of the present invention have made intensiveinvestigations with a view to attaining the foregoing objects. As aresult of those investigations, the inventors of the present inventionhave found out that high-purity isochroman compounds can be obtained inhigh yields when an aqueous solution of formaldehyde having a specificconcentration is used as a formaldehyde source for a cyclizationreaction. The inventors of the present invention have further found outthat isochroman compounds can be prepared directly from aromatichydrocarbon compounds through simple operations when an aqueous solutionof formaldehyde having a specific concentration is used as theformaldehyde source while using the aromatic hydrocarbon compound as thestarting material. The present invention has been completed based onthese findings.

Specifically, the present invention provides a process for preparingisochroman compounds represented by the following general formula (I):##STR3## wherein R₁ and R₂ each stands for a hydrogen atom, a loweralkyl group or a lower alkoxyl group, or alternatively R₁ and R₂ arerespectively bonded to adjacent carbon atoms with mutual bonding of R₁and R₂ together with the carbon atoms respectively bonded to R₁ and R₂to form a benzene ring, a naphthalene ring, or a C₅ or C₆ cycloalkane orcycloalkene which may have 1 to 6 lower alkyl groups; and R₃ stands fora hydrogen atom or a lower alkyl group;

comprising the step of adding an aqueous solution of formaldehyde havinga concentration of 40 to 70 wt. % to a complex of an arylalkanolrepresented by the following general formula (II) with a Friedel-Craftscatalyst to cyclize the arylalkanol: ##STR4## wherein R₁, R₂ and R₃ areeach as defined above.

The foregoing process for preparing isochroman compounds may furthercomprise the step of mixing the arylalkanol of the above-mentionedformula (II) with the Friedel-Crafts catalyst to prepare the complex ofthe arylalkanol with the Friedel-Crafts catalyst.

Alternatively, the process for preparing isochroman compounds mayfurther comprise the step of reacting an aromatic hydrocarbon compoundrepresented by the following general formula (III) with an alkyleneoxide in the presence of the Friedel-Crafts catalyst to prepare thecomplex of the arylalkanol with the Friedel-Crafts catalyst: ##STR5##wherein R₁ and R₂ each stands for a hydrogen atom, a lower alkyl groupor a lower alkoxyl group, or alternatively R₁ and R₂ are respectivelybonded to adjacent carbon atoms with mutual bonding of R₁ and R₂together with the carbon atoms respectively bonded to R₁ and R₂ to forma benzene ring, a naphthalene ring, or a C₅ or C₆ cycloalkane orcycloalkene which may have 1 to 6 lower alkyl groups.

The present invention, which is directed to a process for preparingisochroman compounds represented by the aforementioned formula (I),involves a process comprising the step of reacting an aromatichydrocarbon compound represented by the above-mentioned formula (III)with an alkylene oxide in the presence of a Friedel-Crafts catalyst, andthe step of adding an aqueous solution of formaldehyde having aconcentration of 40 to 70 wt. % to the reaction mixture containing theresulting reaction product (i.e., the complex of the arylalkanol withthe Friedel-Crafts catalyst) to cyclize the reaction product.

The scope and application of the present invention will become apparentfrom the following detailed description and Examples. Since, however,the spirit of the present invention as well as various alterations andmodifications falling within the scope of the present invention would beapparent from the detailed description and Examples to those skilled inthe art, it should be understood that the detailed description andExamples are described only by way of example although they demonstratepreferred embodiments of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

In the aforementioned formulae (I), (II) and (III), the lower alkylgroup in the definition of R₁, R₂ and R₃ refers to a C₁ to C6 linear orbranched alkyl group, specific examples of which include a methyl group,an ethyl group, a propyl group, an isopropyl group, a butyl group, anisobutyl group, a pentyl group, an isopentyl group, a hexyl group, andan isohexyl group. Among them, a methyl group, an ethyl group, and anisopropyl group can be mentioned as preferred examples of the loweralkyl group. On the other hand, the lower alkoxyl group in thedefinition of R₁ and R₂ refers to an alkoxyl group derived from a C₁ toC₆ linear or branched alkyl group, specific examples of which include amethoxy group, an ethoxy group, a propoxy group, an isopropoxy group, abutoxy group, an isobutoxy group, a pentyloxy group, an isopentyloxygroup, a hexyloxy group, and an isohexyloxy group. Among them, a methoxygroup, an ethoxy group, and an isopropoxy group can be mentioned aspreferred examples of the lower alkoxyl group.

In the aforementioned formulae (I), (II) and (III), possible one of thedefinition of R₁ and R₂ to the effect that R₁ and R₂ are respectivelybonded to adjacent carbon atoms with mutual bonding of R₁ and R₂together with the carbon atoms respectively bonded to R₁ and R₂ to forma benzene ring, a naphthalene ring, or a C₅ or C₆ cycloalkane orcycloalkene which may have 1 to 6 lower alkyl groups is intended to meanthat a benzene ring together with R₁ and R₂ in these formulae representsa naphthalene ring, a phenanthrene ring, an anthracene ring, or a1,2,3,4-pentahydronaphthalene ring or indane ring which may have 1 to 6lower alkyl groups in a hydrogenated position(s) thereof. The expression"cycloalkane or cycloalkene" is used herein in order to indicate thatthe benzene ring in the aforementioned formulae may involve either 2carbon atoms bonded to each other through a single bond or 2 carbonatoms bonded to each other through a double bond. The process of thepresent invention is especially preferably applicable to a compoundwherein the C₅ or C₆ cycloalkane or cycloalkene which may have 1 to 6lower alkyl groups is a cyclopentane or cyclohexane having 3 to 6 loweralkyl groups. A benzene ring, a naphthalene ring, or a cycloalkane orcycloalkene, formed by R₁ and R₂ together with the carbon atoms bondedthereto, may jointly own any two mutually adjacent carbon atoms at the5,6-positions, 6,7-positions or 7,8-positions of the isochroman skeletonof the compound represented by the aforementioned formula (I), mayjointly own any two mutually adjacent carbon atoms at the2',3'-positions, 3',4'-positions or 4',5'-positions of the2-phenylalkan-1-ol represented by the aforementioned formula (II), ormay jointly own any two mutually adjacent carbon atoms at the1,2-positions or 2,3-position of the benzene ring of the compoundrepresented by the aforementioned formula (III).

Examples of the isochroman compounds of the aforementioned formula (I)prepared according to the process of the present invention includeisochroman represented by the following formula (A),6-oxa-1,1,2,3,3,8-hexamethyl-2,3,5,6,7,8-hexahydro-1H-benz f!indene(galaxolide) represented by the following formula (B),6-oxa-1,1,3,8-tetramethyl -3-ethyl-2,3,5,6,7,8-hexahydro-1H-benzf!indene represented by the following formula (C), and6-oxa-1,1,3,3,8-pentamethyl -2,3,5,6,7,8-hexahydro-lH-benz f!-indenerepresented by the following formula (D): ##STR6##

Examples of the arylalkanol of the aforementioned formula (II) to beused in the present invention include phenylethyl alcohol represented bythe following formula (i),2-(1',1',2'3',3'-pentamethylindan-5'-yl)-1-propanol represented by thefollowing formula (ii), 2-(1'-ethyl-1,',3',3'-trimethylindan-5'-yl)-1-propanol represented by the following formula (iii), and2-(1,',1',3',3'-tetramethylindan -5'-yl)-l-propanol represented by thefollowing formula (iv): ##STR7##

Examples of the aromatic hydrocarbon compounds of the aforementionedformula (III) to be used in the present invention include benzene, loweralkyl-substituted benzenes, lower alkoxyl-substituted benzenes,naphthalene, antracene, indane, lower alkyl-substituted indanes,tetralin, and lower alkyl-substituted tetralins. Among them, examples ofthe aromatic hydrocarbon compounds to which the process of the presentinvention is suitably applicable include benzene,1,1,2,3,3-pentamethylindane represented by the following formula (a),1,1,3-trimethyl-3-ethylindane represented by the following formula (b),and 1,1,3,3-tetramethylindane represented by the following formula (c):##STR8##

Examples of the Friedel-Crafts catalyst to be used include aluminumchloride, tin tetrachloride, titanium tetrachloride, zinc chloride,aluminum bromide, antimony trichloride, antimony pentachloride, andaluminum iodide, among which aluminum chloride, tin tetrachloride andtitanium tetrachloride are preferred, among which aluminum chloride andtin tetrachloride are especially preferred. The Friedel-Crafts catalystis used preferably in an amount of 0.5 to 1.5 mol, further preferably0.7 to 1.1 mol, per mol of the arylalkanol of the aforementioned formula(II) or the aromatic hydrocarbon compound of the formula (III).

The alkylene oxide that may be used in the present invention is ethyleneoxide or propylene oxide. The use of the alkylene oxide in asubstantially equimolar amount to that of the aromatic hydrocarboncompound of the aformentioned formula (III) will suffice. Alternatively,however, either the alkylene oxide or the aromatic hydrocarbon compoundmay be used in an excessive amount.

The process of the present invention is characterized by comprising thestep of adding an aqueous solution of formaldehyde having aconcentration of 40 to 70 wt. % to the complex of the arylalkanol withthe Friedel-Crafts catalyst to cyclize the arylalkanol. The complex ofthe arylalkanol with the Friedel-Crafts catalyst can be prepared bymixing the arylalkanol with the Friedel-Crafts catalyst. Accordingly,one mode of the process of the present invention comprises the step ofmixing an arylalkanol according to the present invention with aFriedel-Crafts catalyst to prepare the complex of the arylalkanol withthe Friedel-Crafts catalyst, and the step of adding an aqueous solutionof formaldehyde having a concentration of 40 to 70 wt. % to theresulting complex of the arylalkanol with the Friedel-Craft's catalystto cyclize the arylalkanol.

Alternatively, the complex of the arylalkanol with the Friedel-Craftscatalyst may be prepared by reacting the aromatic hydrocarbon compoundof the formula (III) with an alkylene oxide in the presence of theFriedel-Crafts catalyst. Accordingly, another mode of the process of thepresent invention comprises the step of reacting an aromatic hydrocarboncompound according to the present invention with an alkylene oxide inthe presence of a Friedel-Crafts catalyst to prepare a complex of thearylalkanol with the Friedel-Crafts catalyst, and the step of adding anaqueous solution of formaldehyde having a concentration of 40 to 70 wt.% to the resulting complex of the arylalkanol with the Friedel-Craftscatalyst to cyclize the arylalkanol. In this process, the secondcyclization step may be taken even without isolation of the complex ofthe arylalkanol with the Friedel-Crafts catalyst. Accordingly, thisprocess is a simple and economical one.

In the present invention, the reaction of the aromatic hydrocarboncompound with the alkylene oxide may be effected by any known method.This reaction is effected preferably in the presence of a solvent,further preferably in the presence of a chlorinated hydrocarbon solvent.Examples of the chlorinated hydrocarbon solvent include dichloromethaneand dichloroethane, of which dichloromethane is most suitable. Further,this reaction may be effected at a temperature falling within the rangeof -40 to 0° C., preferably -30 to -20 C. When the reaction is effectedat a temperature falling within this range, the rate of reaction issuitable while hardly involving the occurrence of side reactions,whereby a high yield can be attained. The reaction time is preferablyabout 30 minutes to about 5 hours.

In the present invention, the complex of the arylalkanol with theFriedel-Crafts catalyst, after being prepared, is mixed with an aqueoussolution of formaldehyde having a concentration of 40 to 70 wt. %,preferably 40 to 55 wt. %, to cyclize the arylalkanol. As describedabove, the aqueous solution of formaldehyde may be added directly to thereaction mixture of the aromatic hydrocarbon compound according to thepresent invention with the alkylene oxide.

In the present invention, it is important to use an aqueous solution offormaldehyde having a concentration of 40 to 70 wt. When use is made ofan aqueous solution of formaldehyde having a concentration lower than 40wt. %, the operation of reaction is complicated. For example, when useis made of commercially available formalin (a 37 wt. % aqueous solutionof formaldehyde), the reaction mixture gels to deteriorate the yield ofreaction. On the other hand, when use is made of an aqueous solution offormaldehyde having a concentration exceeding 70 wt. %, formaldehyde ispolymerized unfavorably. Further the use of formalin (a 37 wt. % aqueoussolution of formaldehyde) in combination with paraformaldehyde insteadof a high-concentration aqueous solution of formaldehyde, thoughconceivable, entails complicated operations because 2 kinds of startingmaterials are required. The amount of the aqueous solution offormaldehyde to be added is preferably such that the amount offormaldehyde is 0.7 to 1.1 mol per mol of the aromatic hydrocarboncompound of the aforementioned formula (III). The aqueous solution offormaldehyde is added to the complex of the arylalkanol with theFriedel-Crafts catalyst preferably at a temperature of -40° to 20° C.,further preferably -30 to 5° C., especially preferably -30 to 0° C. Thecyclization reaction may be effected at a temperature usually fallingwithin the range of -30 to 30° C., preferably 0 to 30° C. When thereaction is effected at a temperature falling within this range, therate of reaction is suitable while hardly involving the occurrence ofside reactions, whereby a high yield can be attained. The reaction timeis preferably about 1 hour to about 5 hours.

A preferred embodiment of the process of the present invention is asfollows:

A Friedel-Crafts catalyst (e.g., aluminum chloride) and a chlorinatedhydrocarbon solvent (e.g., dichloromethane) are added to an aromatichydrocarbon compound of the aforementioned formula (III) under stirring.The resulting mixture is cooled to a temperature of about -40 to -20° C.Subsequently, a solution of an alkylene oxide in a chlorinatedhydrocarbon solvent (e.g., dichloromethane) is dropwise added to theresulting mixture over 2 to 5 hours. During dropwise addition, thereaction system is maintained at a temperature of about -40 to -20° C.Thereafter, an aqueous solution of formaldehyde having a concentrationof 40 to 70 wt. % is added to the resulting reaction mixture at atemperature of -30 to -20° C. over about 20 to 30 minutes. The reactionis effected under stirring at a predetermined reaction temperature for 2to 3 hours to complete the reaction. Water is added to the reactionproduct to remove the resulting water phase containing theFriedel-Crafts catalyst. The organic phase containing the product iswashed with an aqueous solution of sodium hydroxide (caustic soda)having a concentration of 5 to 10 wt. % under a weakly basic condition.The organic phase containing the product is distilled to remove thesolvent, followed by vacuum distillation. According to the foregoingprocedure, the desired isochroman compound of the aforementioned formula(I) can be obtained in a high yield.

According to the process of the present invention, isochroman compounds,e.g., galaxolides, can be obtained in high yields and in such a highpurity that they are substantially free from unreacted startingmaterials and any by-products (high-boiling substances). The reactionproduct obtained according to the present invention is a substance whichhas such an odor as to be well fit for use as a perfume.

Further, according to the process of the present Invention, introductionof hydrogen chloride gas for the reaction from outside is unnecessary,and unnecessary free hydrogen chloride gas is not substantiallygenerated during the reaction. Accordingly, the process of the presentinvention is characterized in that it is remarkably simple in operationsand involves little corrosion of equipment as compared with conventionalprocesses involving introduction of hydrogen chloride gas from outsideand conventional processes involving generation of hydrogen chloride gasduring the reaction.

Furthermore, in comparison with another conventional process comprisingthe step of adding a compound having a free hydroxyl group as adeactivator to the reaction system in order to deactivate the catalystbefore the addition of formaldehyde, the process of the presentinvention does not require such a deactivator and allows the reaction tobe effected at a low temperature, whereby the post-treatment step can besimplified.

Moreover, according to the process of the present invention, isochromancompounds can be prepared in a single stage of reaction while usingaromatic hydrocarbon compounds as the starting material. Thus, theprocess is simplified in steps as compared with conventional processes.Accordingly, the process of the present invention can be carried outvery economically. Further, according to the process of the presentinvention, isochroman compounds can be prepared in high yields. In thisaspect as well, the process of the present invention is very economical.

EXAMPLES

The following Examples will illustrate the present invention in moredetail, but should not be construed as limiting the scope of the presentinvention.

In Examples, "%" is based on weight unless otherwise specified.

Example 1

75 g (0.398 mol) of 1,1,2,3,3-pentamethylindane was placed in a 500 mlfour-necked flask equipped with a stirrer, a Liebig condenser having theupper portion thereof provided with a calcium chloride tube, and athermometer, then stirred under a nitrogen stream at 300 rpm, and thenmixed with 42.5 g (0.319 mol) of aluminum chloride and 17.3 g ofdichloromethane at room temperature. The resulting solution was cooledto -20° C. A solution of 23.1 g (0.398 mol) of propylene oxide in 146.5g of dichloromethane was dropwise added to the cooled solution over 4hours. During this dropwise addition, the temperature of the reactionsystem was maintained at -20° C. to -30° C. After the completion of thedropwise addition, the resulting mixture was stirred at the sametemperature for 15 minutes. Thereafter, 18 g (0.282 mol) of a 47%aqueous solution of formaldehyde was added to this mixture at 5° C. over30 minutes. The resulting mixture was heated up to a temperature of 20°C. under stirring, and then further stirred at the same temperature for2 hours and 30 minutes. 100 g of water was carefully dropwise added tothe resulting mixture at a temperature of 30° C. or below. The resultingmixture was heated up to a temperature of 40° C. under stirring, andthen further stirred at the same temperature for 1 hour. The resultingreaction mixture was allowed to stand still to effect phase separation.After the removal of the lower layer, the remaining organic phase wasmixed with 50 g of a 10% aqueous solution of caustic soda. The resultingmixture was stirred at 40° C. for 1 hour, and then allowed to standstill to effect phase separation. After the removal of the lower layer,the remaining organic phase was distilled to remove the solvent.Subsequently, the residue was subjected to vacuum distillation (under 2Torr) to obtain 67.2 g (0.26 mol) of 6-oxa-1,1,2,3,3,8-hexamethyl-2,35,6,7,8-hexahydro -1H-benz f!indene as a fraction boiling at 138 to 148°C. (under 2 Torr). The yield was 65%.

Example 2

The reactions were effected in the same manner as in Example 1 exceptthat 83.1 g of tin tetrachloride was used instead of 42.5 g of aluminumchloride. As a result, there was obtained 62.0 g (0.24 mol) of6-oxa-1,1,2,3,3,8-hexamethyl -2,3,5,6,7,8-hexahydro-lH-benz f!indene.The yield was 60%.

Example 3

31 g (0.398 mol) of benzene was put in a 500 ml four-necked flaskequipped with a stirrer, a Liebig condenser having the upper portionthereof provided with a calcium chloride tube, and a thermometer, thenstirred under a nitrogen stream at 300 rpm, and then mixed with 53 g(0.398 mol) of aluminum chloride and 17.3 g of dichlorometahne at roomtemperature. The resulting solution was cooled to -20° C. A solution of17.5 g (0.398 mol) of ethylene oxide in 146.5 g of dichloromethane wasdropwise added to the cooled solution over 4 hours. During this dropwiseaddition, the temperature of the reaction system was maintained at -20°C. to -30° C. After the completion of the dropwise addition, theresulting mixture was stirred at the same temperature for 15 minutes.Thereafter, 18 g (0.282 mol) of a 47% aqueous solution of formaldehydewas added to this mixture at 5° C. over 30 minutes. The resultingmixture was heated up to a temperature of 20° C. under stirring, andthen further stirred at the same temperature for 2 hours and 30 minutes.100 g of water was carefully added dropwise to the resulting mixture ata temperature of 30° C. or below. The resulting mixture was heated up toa temperature of 40° C. under stirring, and then further stirred at thesame temperature for 1 hour. The resulting reaction mixture was allowedto stand still to effect phase separation. After the removal of thelower layer, the remaining organic phase was mixed with 50 g of a 10%aqueous solution of caustic soda. The resulting mixture was stirred at40° C. for 1 hour, and then allowed to stand still to effect phaseseparation. After the removal of the lower layer, the remaining organicphase was distilled to remove the solvent. Subsequently, the residue wassubjected to vacuum distillation (under 20 Torr) to obtain 37.4 g (0.278mol) of isochroman as a fraction boiling at 105 to 106.5° C. (under 20Torr). The yield was 70%.

Example 4

1,1,2,3, 3-Pentamethylindane was mixed with an equimolar amount of ananhydrous aluminum chloride powder. The resulting mixture was cooled toa temperature of -5° C. to -10° C. A solution of propylene oxide in1,1,2,3,3-pentamethylindane was dropwise added to the cooled mixture.Immediately after the completion of the dropwise addition, the resultingbulk product was put into the same volume of iced water under stirring.

After being allowed to stand still to effect phase separation, the upperorganic layer was sequentially washed with a 5% aqueous solution ofcaustic soda and an aqueous solution of sodium chloride. The unreacted1,1,2,3,3-pentamethylindane was removed by vacuum distillation. Thebottom was distilled to obtain 2-(1',1',2',3',3'-pentamethylindanyl-5')propan-1-ol.

50 g (0.203 mol) of 2-(1',1',2',3',3'-pentamethyl-indanyl-5')propan-1-ol and 50 g of dichloromethane were put in a 500 ml four-neckedflask equipped with a stirrer, a Liebig condenser having the upperportion thereof provided with a calcium chloride tube, and athermometer. The resulting solution was stirred, and then mixed with21.7 g (0.16 mol) of aluminum chloride at room temperature. Theresulting solution was cooled to 0° C. 13 g (0.203 mol) of a 47% aqueoussolution of formaldehyde was added to the cooled solution at 0° C. over30 minutes. The resulting mixture was heated up to a temperature of 20°C. under stirring, and then further stirred at the same temperature for2 hours and 30 minutes. 100 g of water was carefully dropwise added tothe resulting mixture at a temperature of 30° C. or below. The resultingmixture was heated up to a temperature of 40° C. under stirring, andthen further stirred at the same temperature for 1 hour. The resultingreaction mixture was allowed to stand still to effect phase separation.After the removal of the lower layer, the remaining organic phase wasmixed with 50 g of a 10% aqueous solution of caustic soda. The resultingmixture was stirred at 40° C. for 1 hour, and then mixed with ether. Theresulting mixture was stirred and then allowed to stand still to effectphase separation. After the removal of the lower layer, the remainingorganic phase was distilled to remove the solvent. Subsequently, theresidue was subjected to vacuum distillation (under 2 Torr) to obtain 50g (0.19 mol) of 6-oxa-1,1,2,3,3,8-hexamethyl-2,3,5,6,7,8-hexahydro-1H-benz f!indene as a fraction boiling at 138 to148° C. (under 2 Torr). The yield was 95%.

Example 5

The reactions were effected in substantially the same manner as inExample 1 except that the 47% aqueous solution of formaldehyde was addedat -20° C. As a result, 6-oxa-1,1,2,3,3,8-hexamethyl-2,3,5,6,7,8-hexahydro-1H-benz f!indene was prepared in a yield of 70%.

Example 6

The reactions were effected in substantially the same manner as inExample 2 except that the 47% aqueous solution of formaldehyde was addedat -20° C. As a result, 6-oxa-1,1,2,3,3,8-hexamethyl-2,3,5,6,7,8-hexahydro-1H-benz f!indene was prepared in a yield of 63%.

Example 7

The reactions were effected in substantially the same manner as inExample 3 except that the 47% aqueous solution of formaldehyde was addedat -20° C. As a result, isochroman was prepared in a yield of 74%.

Example 8

The reactions were effected in substantially the same manner as inExample 4 except that the 47% aqueous solution of formaldehyde was addedat -20° C. As a result, 6-oxa-1,1,2,3,3,8-hexamethyl-2,3,5,6,7,8-hexahydro-1H-benz f!indene was prepared in a yield of 97%.

Comparative Example 1

75 g (0.398 mol) of 1,1,2,3,3-pentamethylindane was put in a 500 mlfour-necked flask equipped with a stirrer, a Liebig condenser having theupper portion thereof provided with a calcium chloride tube, and athermometer, then stirred under a nitrogen stream at 300 rpm, and thenmixed with 42.5 g (0.319 mol) of aluminum chloride and 17.3 g ofdichloromethane at room temperature. The resulting solution was cooledto -20° C. A solution of 23.1 g (0.398 mol) of propylene oxide in 146.5g of dichloromethane was dropwise added to the cooled solution over 4hours. During this dropwise addition, the temperature of the reactionsystem was maintained at -20° C. to -30° C. After the completion of thedropwise addition, the resulting mixture was stirred at the sametemperature for 15 minutes. Thereafter, 8.6 g (0.478 mol) of water wasdropwise added to this mixture at -20° C., followed by the addition of8.4 g (0.266 mol) of paraformaldehyde. The resulting mixture was heatedup to room temperature (22° C.) under stirring, and then further stirredat the same temperature for 3 hours. 90 g of water was added to theresulting reaction mixture. The resulting mixture was heated up to atemperature of 40° C. under stirring, and then further stirred at thesame temperature for 1 hour. The resulting reaction mixture was allowedto stand still to effect phase separation. After the removal of thelower layer, the remaining organic phase was mixed with 50 g of a 10%aqueous solution of caustic soda. The resulting mixture was stirred at40° C. for 1 hour, and then allowed to stand still to effect phaseseparation. After the removal of the lower layer, the remaining organicphase was distilled to remove the solvent. Subsequently, the residue wassubjected to vacuum distillation (under 2 Torr) to obtain 41.3 g (0.16mol) of 6-oxa-1,1,2,3,3,8-hexamethyl -2,3,5,6,7,8-hexahydro-1H-benzf!indene as a fraction boiling at 138 to 148° C. (under 2 Torr). Theyield was 40%.

Comparative Example 2

75 g (0.398 mol) of 1,1,2,3,3-pentamethylindane was put in a 500 m;four-necked flask equipped with a stirrer, a Liebig condenser having theupper portion thereof provided with a calcium chloride tube, and athermometer, then stirred under a nitrogen stream at 300 rpm, and thenmixed with 42.5 g (0.319 mol) of aluminum chloride and 17.3 g ofdichloromethane at room temperature. The resulting solution was cooledto -20° C. A solution of 23.1 g (0.398 mol) of propylene oxide in 146.5g of dichloromethane was dropwise added to the cooled solution over 4hours. During this dropwise addition, the temperature of the reactionsystem was maintained at -20° C. to -30° C. After the completion of thedropwise addition, the resulting mixture was stirred at the sametemperature for 15 minutes. Thereafter, 8.6 g (0.478 mol) of water wasdropwise added to this mixture at -20° C. Subsequently, 8.4 g (0.266mol) of formaldehyde formed by the thermal decomposition ofparaformaldehyde was introduced into the resulting mixture whileeffecting the reaction at room temperature (22° C.) for 3 hours. 90 g ofwater was added to the resulting reaction mixture. The resulting mixturewas heated up to a temperature of 40° C. under stirring, and thenfurther stirred at the same temperature for 1 hour. The resultingreaction mixture was allowed to stand still to effect phase separation.After the removal of the lower layer, the remaining organic phase wasmixed with 50 g of a 10% aqueous solution of caustic soda. The resultingmixture was stirred at 40° C. for 1 hour, and then allowed to standstill to effect phase separation. After the removal of the lower layer,the remaining organic phase was distilled to remove the solvent.Subsequently, the residue was subjected to vacuum distillation (under 2Torr) to obtain 46.5 g (0.18 mol) of 6-oxa-1,1,2,3,3,8-hexamethyl-2,3,5,6,7,8-hexahydro-1H-benz f!indene as a fraction boiling at 138 to148° C. (under 2 Torr). The yield was 45%.

Comparative Example 3

75 g (0.398 mol) of 1,1,2,3,3-pentamethylindane was put in a 500 mlfour-necked flask equipped with a stirrer, a Liebig condenser having theupper portion thereof provided with a calcium chloride tube, and athermometer, then stirred under a nitrogen stream at 300 rpm, and thenmixed with 42.5 g (0.319 mol) of aluminum chloride and 17.3 g ofdichloromethane at room temperature. The resulting solution was cooledto -20° C. A solution of 23.1 g (0.398 mol) of propylene oxide in 146.5g of dichloromethane was dropwise added to the cooled solution over 4hours. During this dropwise addition, the temperature of the reactionsystem was maintained at -20° C. to -30° C. After the completion of thedropwise addition, the resulting mixture was stirred at the sametemperature for 15 minutes. The resulting mixture was heated up to atemperature of 5° C. under stirring. Thereafter, 23 g (0.284 mol) of a37% aqueous solution of formaldehyde was added to this mixture at thesame temperature over 30 minutes. The resulting reaction mixture washeated up to a temperature of 20° C. under stirring, which was difficultbecause the reaction mixture became gel. 90 g of water was added to theresulting reaction mixture. The resulting mixture was heated up to atemperature of 40° C. under stirring, and then further stirred at thesame temperature for 1 hour. The resulting reaction mixture was allowedto stand still to effect phase separation. After the removal of thelower layer, the remaining organic phase was mixed with 50 g of a 10%aqueous solution of caustic soda. The resulting mixture was stirred at40° C. for 1 hour, and then allowed to stand still to effect phaseseparation. After the removal of the lower layer, the remaining organicphase was distilled to remove the solvent. Subsequently, the residue wassubjected to vacuum distillation (under 2 Torr) to obtain 46.5 g (0.18mol) of 6-oxa-1,1,2,3,3,8-hexamethyl-2,3,5,6,7,8-hexahydro-1H-benzf!indene as a fraction boiling at 138 to 148° C. (under 2 Torr). Theyield was 45%.

We claim:
 1. A process for preparing isochroman compounds represented bythe following general formula (I): ##STR9## wherein R₁ and R₂ eachstands for a hydrogen atom, a lower alkyl group or a lower alkoxylgroup, or alternatively R₁ and R₂ are respectively bonded to adjacentcarbon atoms with mutual bonding of R₁ and R₂ together with the carbonatoms respectively bonded to R₁ and R₂ to form a benzene ring, anaphthalene ring, or a C₅ or C₆ cycloalkane or cycloalkene which mayhave 1 to 6 lower alkyl groups; and R₃ stands for a hydrogen atom or alower alkyl group;comprising the step of adding an aqueous solution offormaldehyde having a concentration of 40 to 70 wt. % to a complex of anarylalkanol represented by the following general formula (II) with aFriedel-Crafts catalyst to cyclize said arylalkanol: ##STR10## whereinR₁, R₂ and R₃ are each as defined above.
 2. A process as claimed inclaim 1, wherein said Friedel-Crafts catalyst is aluminum chloride, tintetrachloride, or titanium tetrachloride.
 3. A process as claimed inclaim 1, which further comprises the step of mixing said arylalkanol ofthe formula (II) with said Friedel-Crafts catalyst to prepare saidcomplex of said arylalkanol with said Friedel-Crafts catalyst.
 4. Aprocess as claimed in claim 1, which further comprises the step ofreacting an aromatic hydrocarbon compound represented by the followinggeneral formula (III) with an alkylene oxide in the presence of saidFriedel-Crafts catalyst to prepare said complex of said arylalkanol withsaid Friedel-Crafts catalyst: ##STR11## wherein R₁ and R₂ each standsfor a hydrogen atom, a lower alkyl group or a lower alkoxyl group, oralternatively R₁ and R₂ are respectively bonded to adjacent carbon atomswith mutual bonding of R₁ and R₂ together with the carbon atomsrespectively bonded to R₁ and R₂ to form a benzene ring, a naphthalenering, or a C₅ or C₆ cycloalkane or cycloalkene which may have 1 to 6lower alkyl groups.
 5. A process as claimed in claim 4, wherein saidaromatic carbon compound represented by the formula (III) is zene,1,1,2,3,3-pentamethylindane represented by the following formula (a),1,1,3-trimethyl-3-ethylindane resented by the following formula (b), or1,1,3,3-tetramethylindane represented by the following formula (c):##STR12##
 6. A process as claimed in claim 4, wherein said alkylene isethylene oxide or propylene oxide.